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1.
Gene Ther ; 22(3): 217-26, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25567536

RESUMO

The CD40/CD154 co-stimulatory pathway is crucial in alloimmune response. We developed a novel small interfering RNA (siRNA) delivery system with a poly-dA extension at the 5'-end of the siRNA sense strand that was stably incorporated into 1,3-ß-glucan (schizophyllan, SPG). This was captured and incorporated into dendritic cells (DCs) through its receptor, Dectin-1, specifically silencing CD40 genes (siCD40) to exert immunoregulatory activity. siCD40/SPG-treated CBA mice permanently accepted B10 fully mismatched cardiac allografts. Consistent with graft survival, the infiltration of CD4(+), CD8(+) T cells into the graft was lower, and that the numbers of CD40(low)CD11c(+) DCs cells and CD4(+)Foxp3(+)cells were increased in both the graft and in the recipient spleen. In addition, naive CBA recipients given an adoptive transfer of splenocytes from the primary recipients with siCD40/SPG accepted a heart graft from donor-type B10, but not third-party Balb/c mice. In conclusion, the treatment with siCD40/SPG targeting DCs could generate antigen-specific Tregs, resulting in the permanent acceptance of mouse cardiac allografts. These findings have important implications for clarifying the mechanism underlying the induction of tolerance in DCs, and also highlight the potential of immunomodulation and the feasibility of siRNA-based clinical therapy in the transplantation field.


Assuntos
Adjuvantes Imunológicos/metabolismo , Aloenxertos/fisiologia , Antígenos CD40/metabolismo , Transplante de Coração , Células Mieloides/metabolismo , RNA Interferente Pequeno/metabolismo , Sizofirano/metabolismo , Adjuvantes Imunológicos/química , Aloenxertos/citologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , Sizofirano/química , Subpopulações de Linfócitos T/imunologia , Transfecção
2.
Transplant Proc ; 41(1): 52-4, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19249473

RESUMO

Ischemia/reperfusion (I/R) injury, which induces extensive loss of tubular epithelial cells, is associated with delayed graft function following kidney transplantation. Recent reports have suggested that cell death by I/R injury occurs by autophagy, a cellular degradation process responsible for the turnover of unnecessary or dysfunctional organelles and cytoplasmic proteins, as well as by apoptosis. Recently, we demonstrated that overexpression of the anti-apoptotic factor, Bcl-2, inhibited tubular apoptosis and subsequent tubulointerstitial damage after I/R injury. Autophagy is also observed in cells undergoing cell death in several diseases. Therefore, we hypothesized that increased Bcl-2 protein may protect tubular epithelial cells by suppressing autophagy and inhibiting apoptosis. In the present study, a transgenic mouse model (LC3-GFP TG) in which autophagosomes are labeled with LC3-GFP and Bcl-2/LC3-GFP double transgenic mice (Bcl-2/LC3-GFP TG) were used to examine the effect of Bcl-2 on I/R-induced autophagy. I/R injury, which is associated with marked disruption of normal tubular morphology, promoted the formation of LC3-GFP dots, representing extensively induced autophagosomes. On electron microscopy, the autophagosomes contained mitochondria in I/R-injured tubular epithelial cells. In contrast, Bcl-2 augmentation suppressed the formation of autophagosomes and there was less tubular damage. In conclusion, Bcl-2 augmentation protected renal tubular epithelial cells from I/R injury by suppressing autophagosomal degradation and inhibiting tubular apoptosis.


Assuntos
Traumatismo por Reperfusão/prevenção & controle , Animais , Autofagia/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Epiteliais/fisiologia , Genes Reporter , Genes bcl-2 , Humanos , Camundongos , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-bcl-2/uso terapêutico , Piruvato Quinase/genética , Ratos , Traumatismo por Reperfusão/patologia
3.
Am J Transplant ; 8(10): 2004-14, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18727698

RESUMO

The ultimate goal of organ transplantation is to establish graft tolerance where CD4+CD25+FOXP3+ regulatory T (Treg) cells play an important role. We examined whether a superagonistic monoclonal antibody specific for CD28 (CD28 SA), which expands Treg cells in vivo, would prevent acute rejection and induce tolerance using our established rat acute renal allograft model (Wistar to Lewis). In the untreated or mouse IgG-treated recipients, graft function significantly deteriorated with marked destruction of renal tissue, and all rats died by 13 days with severe azotemia. In contrast, 90% of recipients treated with CD28 SA survived over 100 days, and 70% survived with well-preserved graft function until graft recovery at 180 days. Analysis by flow cytometry and immunohistochemistry demonstrated that CD28 SA induced marked infiltration of FOXP3+ Treg cells into the allografts. Furthermore, these long-surviving recipients showed donor-specific tolerance, accepting secondary (donor-matched) Wistar cardiac allografts, but acutely rejecting third-party BN allografts. We further demonstrated that adoptive transfer of CD4+CD25+ Treg cells, purified from CD28 SA-treated Lewis rats, significantly prolonged allograft survival and succeeded in inducing donor-specific tolerance. In conclusion, CD28 SA treatment successfully induces donor-specific tolerance with the involvement of Treg cells, and thus the therapeutic value of this approach warrants further investigation and preclinical studies.


Assuntos
Antígenos CD28/imunologia , Tolerância Imunológica/imunologia , Transplante de Rim/métodos , Animais , Antígenos CD28/química , Linfócitos T CD4-Positivos/metabolismo , Citometria de Fluxo/métodos , Fatores de Transcrição Forkhead/biossíntese , Sobrevivência de Enxerto , Imunoglobulina G/metabolismo , Imuno-Histoquímica/métodos , Subunidade alfa de Receptor de Interleucina-2/biossíntese , Masculino , Camundongos , Ratos , Ratos Endogâmicos Lew , Ratos Wistar , Linfócitos T Reguladores/imunologia
4.
Transplant Proc ; 40(5): 1362-5, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18589106

RESUMO

INTRODUCTION: To achieve a high graft survival rate, patient adherence to immunosuppressive therapy is critical. It is extremely difficult to establish the actual adherence status of transplant recipients; only a few surveys on the issue have been performed in Japan. METHODS: We conducted a questionnaire survey mainly on treatment adherence to calcineurin inhibitors among renal transplant recipients. RESULTS: The survey demonstrated some degree of nonadherence in a relatively high percentage of the patients. The adherence rate was significantly lower for the evening than the morning dose (McNemar test, P < .001). It significantly decreased with time following transplantation for both the morning and the evening doses (logistic regression analysis, P = .025 and <.001, respectively). CONCLUSIONS: Immunosuppressive treatment places a substantial burden on patients, some of whom cannot continue regular treatment at specified time points due to daily life restrictions after they have returned to work.


Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Cooperação do Paciente/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores de Calcineurina , Esquema de Medicação , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Análise de Regressão , Inquéritos e Questionários
5.
Transplant Proc ; 50(4): 1074-1076, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731068

RESUMO

BACKGROUND: Immunocomplex capture fluorescence analysis (ICFA) detects donor-specific antihuman leukocyte antigen (HLA) antibodies (DSA), but the detection sensitivity of HLA class II antibodies using conventional ICFA is as low as 57%. The aim of the study was to improve the detection sensitivity of HLA class II antibodies by ICFA, and compare the ICFA results with the Luminex single-antigen bead test. METHODS: Six DSA-negative kidney transplant donors and recipient pairs and 10 HLA class II DSA-positive pairs were included in the study. The detection sensitivity of modified ICFA was compared with conventional ICFA, and the ICFA results were compared with the Luminex single-antigen bead test. RESULTS: The index value of modified ICFA was higher than that of conventional ICFA. The cutoff value of conventional ICFA was 30,686 (MFI), which was improved to 19,405 using modified ICFA. Regarding the HLA-DQ antibody, 5 samples found to be positive by Luminex single-antigen bead testing were all negative using modified ICFA. The reason for this discrepancy could be related to: (1) the difference in detection sensitivity; (2) the difference in HLA antigen surface expression between naive lymphocytes and synthetic beads; or (3) the structure of synthetic HLA DQ antigen on the Luminex single-antigen beads. CONCLUSION: The index value of the modified ICFA was higher than that of conventional ICFA, and the detection sensitivity of HLA class II antibodies was improved by modified ICFA. Further assessment is necessary to clarify the reasons for divergence between ICFA and Luminex single-antigen bead test results.


Assuntos
Antígenos de Histocompatibilidade Classe II/imunologia , Teste de Histocompatibilidade/métodos , Imunoensaio/métodos , Transplante de Rim , Adulto , Anticorpos/imunologia , Feminino , Imunofluorescência/métodos , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos
6.
Transplant Proc ; 50(8): 2545-2547, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30316395

RESUMO

PURPOSE: Renal transplant patients with vascular rejection type acute T cell-mediated rejection (ATCMR) grade II have a poor prognosis. Vascular lesions in those cases are thought to randomly occur, thus we searched for a novel pathological marker related to vascular rejection in kidney transplantation. METHODS: We determined pathological characteristics in 14 ATCMR grade II patients treated during an acute phase from 2004 to 2013. We then examined whether those findings appeared in transplant kidney biopsy specimens, except for cases of vascular rejection, in patients examined from 2010 to 2014. RESULTS: In 9 of the 14 ATCMR grade II patients, phlebitis was accompanied by inflammatory cells that formed polypoid projections in the venous lumen and partial disappearance of vascular endothelium. Further investigation showed those inflammatory cells to be T cells and macrophages. Histological findings revealed coexisting phlebitis in 2 of 13 patients with ATCMR grade I, 3 of 24 with borderline changes, and none with normal findings. Phlebitis occurred at a significantly greater rate than the other findings in cases of vascular rejection (P < .05). However, there was no significant difference in regard to graft survival between patients with and without phlebitis (P = .1829). CONCLUSION: Our results suggest severe phlebitis as a novel finding associated with the pathology of vascular rejection in patients with a renal allograft.


Assuntos
Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Transplante de Rim/efeitos adversos , Flebite/complicações , Adulto , Feminino , Sobrevivência de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Flebite/patologia , Linfócitos T/imunologia , Transplante Homólogo
7.
Transplant Proc ; 49(1): 145-152, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28104123

RESUMO

BACKGROUND: Renal fibrosis (RF) is a well-known marker for chronic kidney disease (CKD) progression, including chronic renal injury after renal transplantation. However, invasive biopsy is an available examination for evaluation of RF. Diffusion MRI was once recognized as a promising option for RF. However, it is now controversial for RF evaluation in a unilateral ureteral obstruction (UUO) model. METHODS: To seek an optimal imaging method applicable for RF in UUO model kidneys, we attempted a series of MRI methods, including proton density-weighted imaging, T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging, diffusion-weighted imaging, and diffusion tensor imaging (DTI). RESULTS: We identified DTI MRI by spin-echo sequence plus a special kidney attachment as the best option for evaluation of renal UUO fibrosis, compared with normal kidney on the opposite side. To confirm these results, we applied this technique to a rat UUO therapeutic model with the anti-fibrotic reagent Fasudil. Fractional anisotropy values calculated from DTI MRI showed statistically significant linear correlation with the RF area measured by use of Sirius red or Masson trichrome staining of the positive area [cortex (r = 0.6397, P = .0283) and outer stripe of the outer medulla (r = 0.7810, P = .0039)]. CONCLUSIONS: By use of the DTI MRI with spin-echo sequence, it may be possible to accurately evaluate RF in CKD.


Assuntos
Imagem de Tensor de Difusão/métodos , Nefropatias/patologia , Imageamento por Ressonância Magnética/métodos , Animais , Modelos Animais de Doenças , Progressão da Doença , Fibrose/patologia , Masculino , Ratos
8.
Transplant Proc ; 48(3): 781-5, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27234735

RESUMO

BACKGROUND: Utilization of everolimus (EVR) has been increasing in recent years for patients undergoing renal transplantation to reduce calcineurin inhibitor (CNI) levels. However, an optimum regimen has yet to be established. METHODS: We retrospectively examined 12 renal transplant recipients who underwent an induction immunosuppressive protocol; the protocol comprises 5 agents, including EVR plus low-dose tacrolimus extended-release (TAC-ER) treatment. We compared those findings from those of 14 patients who underwent a conventional protocol without EVR. Clinical outcome and pathologic changes were assessed by using protocol graft biopsy findings obtained at 3 months and 1 year after transplantation. RESULTS: The estimated glomerular filtration rate was significantly higher for the EVR group at both 3 months and 1 year compared with the conventional group (P < .01 and P = .03, respectively). TAC-ER trough levels were also significantly lower at 3 months and 1 year (both, P < .01). Histologic findings of the 3-month protocol biopsy samples in the EVR group revealed 4 cases of borderline change and 2 of acute cellular-mediated rejection. The findings from the 1-year biopsy samples revealed 10 cases with normal findings with no evidence of CNI toxicity. Patients in the EVR group developed subclinical borderline change and acute cellular-mediated rejection after 3 months at a significantly higher rate than the conventional group (P = .02). CONCLUSIONS: Use of the present therapeutic strategy successfully maintained the trough of each drug at a lower level, and it also kept renal function stable up to 1 year after transplantation.


Assuntos
Everolimo/uso terapêutico , Sobrevivência de Enxerto , Imunossupressores/uso terapêutico , Transplante de Rim , Tacrolimo/uso terapêutico , Adulto , Idoso , Preparações de Ação Retardada/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
9.
Transplant Proc ; 48(3): 878-83, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27234757

RESUMO

BACKGROUND: Post-transplant anemia (PTA) is a risk factor for mortality and graft loss in kidney transplant patients. METHODS: In all, 172 patients were included in this study. PTA was defined as hemoglobin <13.0 g/dL in men and 12.0 g/dL in women. The primary outcome of interest was the renal outcome, defined as a 50% increase in serum levels of creatinine, a return to chronic dialysis, and subsequent kidney transplantation (KTx). The secondary outcome was a composite of the primary outcome and death. RESULTS: At baseline, 75 patients (43.6%) had PTA. During follow-up of a median of 7.3 years, 52 patients (30.2%) had 2-fold higher creatinine levels than at baseline, 24 patients (14.0%) had to return to chronic dialysis or subsequent KTx, and 11 patients (6.4%) died; 8 (4.7%) of the deceased patients had functioning allografts. Univariate regression analyses showed that a lower hemoglobin level and positive proteinuria were significantly associated with both outcomes. After adjusting for important clinical variables, a lower hemoglobin level remained a strong predictor for both outcomes. Restricted cubic splines showed an almost linear inverse association with a hemoglobin level ≥12 g/dL. The risk of the outcomes increased with decreasing tertiles of the baseline hemoglobin level for both men and women, but the associations in women were much weaker than those in men, suggesting a different prognostic value of the hemoglobin level between men and women. CONCLUSIONS: PTA strongly influenced the renal and patient outcomes in living kidney transplant patients.


Assuntos
Anemia/etiologia , Creatinina/sangue , Hemoglobinas/metabolismo , Transplante de Rim/efeitos adversos , Doadores Vivos , Adulto , Anemia/sangue , Anemia/mortalidade , Feminino , Humanos , Japão/epidemiologia , Transplante de Rim/mortalidade , Masculino , Prognóstico , Fatores de Risco , Taxa de Sobrevida/tendências
10.
Transplant Proc ; 48(3): 890-2, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27234760

RESUMO

OBJECTIVES: Current adherence to dietary recommendations for chronic kidney disease was evaluated in kidney transplant patients in the maintenance phase. METHODS: A total of 268 maintenance phase kidney transplant patients were included in the study. Estimated daily intakes of oral protein and salt were calculated from 24-h urinary excretion of nitrogen and sodium, respectively. Dietary recommendations for chronic kidney disease, as issued in 2014 by the Japanese Society of Nephrology, were used as the basis for assessing diet. RESULTS: The study included 114 female patients and 154 male patients. The mean age, posttransplantation years, body mass index, estimated glomerular filtration rate, and 24-h urinary excretion of protein were 56.3 years, 11.2 years, 22.0 kg/m(2), 42.6 mL/min/1.73 m(2), and 321 mg/d, respectively. Estimated daily protein and salt intakes were 0.98 ± 0.26 g/kg/d and 9.3 ± 3.9 g/d. Only 47 patients (17.5%) in the case of salt intake and 105 patients (39.2%) in the case of protein intake were within reference values. The 24-h urinary protein excretion of the daily salt intake-adherent group (<6 g) was significantly less than that of the nonadherent group (≥6 g) (P = .021). CONCLUSIONS: The adherence rate to dietary recommendations for chronic kidney disease in kidney transplant patients was low. The 24-h urinary protein excretion of the daily salt intake-adherent group was significantly less than that of the nonadherent group. Dietary therapy for these patients may have the potential to improve kidney graft function and survival.


Assuntos
Dieta/normas , Taxa de Filtração Glomerular/fisiologia , Fidelidade a Diretrizes , Transplante de Rim , Insuficiência Renal Crônica/dietoterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Sódio/urina
11.
Transplant Proc ; 37(5): 2131-4, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15964360

RESUMO

BACKGROUND: Chronic allograft nephropathy (CAN) is the main cause of renal transplant failure in the first decade posttransplant. The precise pathogenetic mechanism for CAN is not completely understood. A possible role of renin-angiotensin system for CAN has been suggested through clinical observations that angiotensin-converting enzyme inhibition and angiotensin II receptor blockers prevent CAN. METHODS: Distribution of renin-positive cells in allograft biopsy specimens was examined immunohistochemically in 23 renal transplant recipients diagnosed with CAN Biopsy specimens obtained from seven recipients with stable renal function were examined as controls. Histologic evaluation was performed based on the Banff 97 classification. RESULTS: Renin-positive cells were found in the juxtaglomerular apparatus (JGA) adjoining the afferent arterioles in both groups. When the number of renin-positive cells in JGA was defined as a renin index, it was significantly higher in the CAN than the control group (P = .007). There was no significant difference in age, interval between transplantation and biopsy, and blood pressure between groups. Only a significantly higher serum creatinine was found in the CAN group. CONCLUSIONS: The increased renin-positive cells in JGA suggest a significant role of the intrarenal renin-angiotensin system activation in the development of CAN.


Assuntos
Transplante de Rim/patologia , Renina/metabolismo , Adulto , Biomarcadores/análise , Doença Crônica , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Imunossupressores/classificação , Imunossupressores/uso terapêutico , Transplante de Rim/fisiologia , Masculino , Proteinúria , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo
12.
Transplant Proc ; 47(3): 672-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25891708

RESUMO

BACKGROUND: Lipid abnormalities (LA) are related to an increased risk for cardiovascular diseases in kidney transplantation patients. PATIENTS AND METHODS: Multivariable logistic regression models were used to estimate the risk of LA associated with potential risk factors, including immunosuppressant use, patient background characteristics, and laboratory data. RESULTS: In total, 386 patients who were undergoing kidney transplantation were included in the study. Statins were prescribed to 43% of patients. The LA composite outcome was defined as statin use and/or low density lipoprotein cholesterol level ≥120 mg/dL, and 229 patients (59.3%) developed LA as a result. LA was significantly related to everolimus, corticosteroid, age, and estimated glomerular filtration ratio in the multiple logistic regression analysis. The odds ratios were 2.264, 3.119, 1.186, and 0.870, respectively. Mycophenolate mofetil, mizoribine, azathioprine, cyclosporine (CYA), tacrolimus, proteinuria, body mass index, and male sex were not related to LA. DISCUSSION: CYA influenced lipid metabolism but was not related to LA in our study. The mean post transplantation period was 8.4 years, and the CYA dose decreased over time. The CYA blood concentration was 70.0 ng/mL, which is relatively low, but it decreased the susceptibility to LA. Serum lipid levels were well controlled by statins, and the estimated glomerular filtration rate was maintained stably. CONCLUSIONS: Everolimus and corticosteroid use, as well as a lower estimated glomerular filtration rate and higher age, were significant risk factors for LA. CYA is known for its adverse LA effects, but it was not a significant risk factor for LA in patients undergoing maintenance phase kidney transplantation.


Assuntos
Dislipidemias/epidemiologia , Dislipidemias/etiologia , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Lipídeos/sangue , Corticosteroides/efeitos adversos , Corticosteroides/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Azatioprina/efeitos adversos , Azatioprina/sangue , Ciclosporina/efeitos adversos , Ciclosporina/sangue , Everolimo/efeitos adversos , Everolimo/sangue , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunossupressores/sangue , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/sangue , Ribonucleosídeos/efeitos adversos , Ribonucleosídeos/sangue , Fatores de Risco , Tacrolimo/efeitos adversos , Tacrolimo/sangue
13.
J Interferon Cytokine Res ; 17(6): 369-73, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9198004

RESUMO

The Fas system-based rejection mechanism has not been studied well in terms of cytotoxic T cell activity in graft rejection. We investigated the Fas and Fas ligand level in renal grafts with acute and chronic rejection in a rat model using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Fas ligand in renal allografts was detected as early as 1 day after transplantation in an acute rejection model. It was highly expressed at day 4 and began to decline at day 6 after transplantation. In contrast, Fas ligand in normal kidneys was almost undetectable. Fas ligand in isografts was increased, but the expression level was much lower than in allografts. Interestingly, when Fas ligand expression began to decline in renal allografts, it increased in the spleens of recipients. Fas ligand expression in chronically rejecting allografts was slightly increased, but it was stronger than in isografts. In contrast to Fas ligand gene expression, Fas was constitutively expressed in isografts, allografts, and normal kidneys. However, the Fas level in renal allografts was higher than in normal kidneys. Our data demonstrated that the Fas system might play an important role in acute and chronic rejection by causing apoptosis, and the spleen may eliminate the lymphocytes strongly expressing Fas ligand after completion of the acute rejection.


Assuntos
Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Glicoproteínas de Membrana/biossíntese , Receptor fas/biossíntese , Doença Aguda , Animais , Antígenos de Superfície , Doença Crônica , Proteína Ligante Fas , Rejeição de Enxerto/metabolismo , Rim/imunologia , Rim/metabolismo , Ligantes , Masculino , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , RNA Mensageiro/química , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Baço/imunologia , Baço/metabolismo , Receptor fas/imunologia , Receptor fas/metabolismo
14.
Atherosclerosis ; 158(2): 417-23, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11583721

RESUMO

Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patient's prognosis. In study 1, the effects of immunosuppressants, cyclosporine (CsA) and tacrolimus on serum lipids were compared in-patients undergoing renal transplantation. The study included 32 cases of renal transplantation recipients who randomized to the CsA treatment group (15 patients) and the tacrolimus group (17 patients). Before and 1 month after the transplantation, we assessed the serum lipid levels, apolipoprotein levels, the concentrations of cholesterol in the respective lipoprotein fractions and the enzyme activities related to lipid-metabolism. The serum lipid levels in both groups were significantly increased at 1 month after renal transplantation. In the CsA group, there were significant increases in cholesterol contents in very-low-density lipoprotein (VLDL), LDL2 and HDL2 fractions, whereas, in the tacrolimus group, cholesterol content was increased in VLDL and HDL2 fractions. In study 2, 1 month after renal transplantation, 19 patients with hypercholesterolemia (total cholesterol (TC) >200 mg/dl) and hypertriglyceridemia (triglyceride (TG) >150 mg/dl) were treated with simvastatin 5-10 mg/day for 6 months. Simvastatin treatment significantly decreased serum TC (240+/-29-200+/-22 mg/dl, P<0.001), low-density lipoprotein cholesterol (LDL-C; 114+/-20-99+/-17 mg/dl, P<0.05) and TG levels (217+/-103-130+/-38 mg/dl, P<0.01). In addition, there were significant decreases in very-low-density lipoprotein cholesterol (VLDL-C; 53+/-20-34+/-15 mg/dl, P<0.001). The Cmax and AUC of simvastatin were increased about eight-fold, when simvastatin was given in combination with CsA. In contrast, no significant changes in simvastatin levels were observed when combination with tacrolimus. Although simvastatin levels were increased with CsA, there were no abnormal changes in renal and liver functions, creatinine phosphokinase (CPK) levels or in incidence of adverse effects.


Assuntos
Ciclosporina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Lipídeos/sangue , Sinvastatina/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Apolipoproteínas/sangue , Colesterol/sangue , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Lipoproteínas/sangue , Masculino , Estudos Prospectivos
15.
Ann Thorac Surg ; 70(5): 1634-40, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11093500

RESUMO

BACKGROUND: Little is known about the biological nature of T4 esophageal carcinoma growth signals and host defenses. METHODS: Paraffin-embedded sections from 78 patients with T2 to T4 esophageal squamous cell carcinoma who underwent operation were analyzed with immunohistochemistry. RESULTS: Positive cyclin A showed a significantly greater increase in T4 tumors than in those of other stages, and negative p27 showed a significantly greater decrease in T4 tumors than in large T3 stage tumors (tumor size > or = 4.0 cm). Patients with low-grade tumor-infiltrating lymphocyte (TIL) density showed a significantly greater decrease in T4 than in T2. The combination of p27 and cyclin A was a significant independent prognostic factor among T and N factors in multivariate analysis. TIL density was an independent prognostic factor among immunonutritional variables such as serum albumin concentration and the number of total blood lymphocytes. CONCLUSIONS: T4 esophageal squamous cell carcinoma has a poor prognosis, which is associated with increased p27-negative and cyclin A-positive growth signals in the tumor and with low TIL density in the host.


Assuntos
Biomarcadores/análise , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Ciclina A/análise , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Linfócitos do Interstício Tumoral/patologia , Antígeno Nuclear de Célula em Proliferação/análise , Apoptose , Contagem de Células , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
16.
Transplant Proc ; 36(5): 1314-6, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15251321

RESUMO

BACKGROUND: The recurrence rate of IgA nephropathy (IgAN) in transplanted kidneys has been reported to be >50%. Although recurrent IgAN has a benign clinical course, recent data suggest that it leads to graft loss in a substantial number of patients. METHODS: We performed a retrospective single-center analysis of 34 renal transplant recipients, with biopsy-proven IgAN as the cause of end-stage renal failure. RESULTS: Renal allograft biopsies were performed in 30 patients, of whom 24 did and 6 did not have biopsy-confirmed recurrent transplant IgAN. Recurrent transplant IgAN was more often detected in men and at later timepoints after post-transplantation. Four patients with recurrent transplant IgAN progressed to graft failure. Progression to graft failure was associated with worsened renal function, higher systolic blood pressure, and the lack of presenation of angiotensin-converting enzyme inhibitors (ACEs) at the time of allograft biopsy. Immunologic factors such as frequency of acute rejection, HLA typing, and immunosuppression did not show a relation to recurrence or graft loss. CONCLUSIONS: Recurrent transplant IgAN increased with long-term graft survival and risk factors for graft loss due to recurrent IgAN were similar to those among IgAN in native kidneys.


Assuntos
Glomerulonefrite por IGA/cirurgia , Transplante de Rim/patologia , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Biópsia , Feminino , Glomerulonefrite por IGA/patologia , Teste de Histocompatibilidade , Humanos , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Masculino , Recidiva , Diálise Renal , Análise de Sobrevida , Falha de Tratamento
17.
Transplant Proc ; 36(2 Suppl): 456S-460S, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15041387

RESUMO

A crossover administration of Neoral and Sandimmune was performed in 43 renal allograft recipients who had been on cyclosporine maintenance therapy for 2 to 19 years posttransplant to investigate the pharmacokinetics of cyclosporine. Although there was no difference in C0 values (trough values) when Neoral and Sandimmune were administered at the same doses, AUC(0-4) and AUC(0-12) values of Neoral were 1.57- and 1.36-fold greater than those of Sandimmune, respectively. For both Neoral and Sandimmune, there was a high correlation between the C2 value and AUC(0-4). The Pearson's product-moment coefficient for the correlation between the C2 value and AUC(0-4) was R=0.91642. On the other hand, the correlation with the C0 value (trough value) was low (R=0.53181). During the period of the study, there was no acute rejection episode, onset of adverse drug reaction symptoms, or marked change in laboratory test values.


Assuntos
Ciclosporina/farmacocinética , Adulto , Área Sob a Curva , Química Farmacêutica , Ciclosporina/sangue , Ciclosporina/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Transplante de Rim/imunologia , Transplante de Rim/fisiologia , Masculino , Pessoa de Meia-Idade
18.
J Int Med Res ; 32(1): 45-52, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-14997705

RESUMO

Patients undergoing haemodialysis are predisposed to serum lipid abnormalities that can accelerate the development of atherosclerosis. Serum lipid levels must therefore be controlled over a long period. For patients with reduced renal function (including dialysis patients), special attention must be paid to hyperlipidaemia therapy, particularly drug selection. In this study, 30 mg/day fluvastatin was administered orally to five patients receiving maintenance haemodialysis. Their serum lipid levels and blood biochemistry were monitored during the 6 months of fluvastatin administration, and the pharmacokinetic parameters calculated. The therapeutic efficacy and safety of fluvastatin were demonstrated in this patient group. Furthermore, fluvastatin is not influenced by the dialysis membrane and does not accumulate in haemodialysis patients with hyperlipidaemia.


Assuntos
Anticolesterolemiantes/farmacocinética , Anticolesterolemiantes/uso terapêutico , Ácidos Graxos Monoinsaturados/farmacocinética , Ácidos Graxos Monoinsaturados/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Indóis/farmacocinética , Indóis/uso terapêutico , Falência Renal Crônica/terapia , Diálise Renal , Anticolesterolemiantes/efeitos adversos , Ácidos Graxos Monoinsaturados/efeitos adversos , Fluvastatina , Meia-Vida , Humanos , Hipercolesterolemia/complicações , Indóis/efeitos adversos , Falência Renal Crônica/complicações
19.
Hinyokika Kiyo ; 46(9): 657-61, 2000 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-11107539

RESUMO

Renovascular disease is one of the most common causes of secondary hypertension. Recent technical advances have changed the management principles, which include a more aggressive approach to the diagnosis and treatment of renovascular hypertension (RVH). We experienced a total of 95 cases with RVH between 1958 and 1999. The mean age of all patients was 31.8 years old, ranging from 3 to 64 years. The three major basal diseases that caused RVH were fibromuscular dysplasia (34/95), arteriosclerosis (26/95), and aortitis (12/95). Ninety-two kidneys were treated in 79 of the 95 patients. The major therapeutic modalities performed were reconstruction of renal artery (6/79), nephrectomy (21/79), autotransplantation (26/79), and percutaneous transluminal angioplasty (PTA) (25/79). PTA is now the treatment of choice for the initial management of patients with RVH. Surgical treatment is generally reserved for patients in whom PTA fails. Pharmacotherapy is used on patients awaiting angioplasty or revascularization, those who are too ill for intervention, and those who have failed to respond to intervention.


Assuntos
Angioplastia com Balão , Hipertensão Renovascular/terapia , Nefrectomia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Hipertensão Renovascular/cirurgia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Radiografia , Artéria Renal/diagnóstico por imagem , Artéria Renal/cirurgia
20.
Hinyokika Kiyo ; 41(3): 213-7, 1995 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-7741075

RESUMO

We report here a case of post-biopsy arterio-venous fistula in a renal allograft which was successfully embolized. Percutaneous needle biopsy of renal allograft is performed when the cause of deteriorating renal function is clinically difficult to diagnose, and the pathological diagnosis obtained by it determines the therapy. An easy and safe biopsy encourages the clinician, but some complications occur after the procedure. Arterio-venous fistula is one of the complications after percutaneous needle biopsy of renal allograft. Color-coded ultrasonography is effective to find it, and transarterial embolization should be tried first to treat it.


Assuntos
Fístula Arteriovenosa/etiologia , Biópsia por Agulha/efeitos adversos , Transplante de Rim , Rim/patologia , Artéria Renal , Veias Renais , Adulto , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Embolização Terapêutica , Humanos , Masculino , Ultrassonografia
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